The relatedness of the avian reticuloendotheliosis (RE) viruses to mammalian type C retroviruses is under investigation. Replication in mammalian cells of the helper virus (REV-A), present in oncogenic preparations of reticuloendotheliosis virus, has been observed and confirmed by a variety of methods including immunogeldiffusion, gel electrophoresis, peptide mapping, viral interference, oncogene rescue, and immune inhibition of viral DNA polymerases. The active site of the DNA polymerase of REV-A was shown to exhibit an antigenic determinant shared with the DNA polymerases of mammalian type C retroviruses. This determinant is not detectable at the active sites of polymerases from types B or D mammalian retroviruses or avian myeloblastosis virus. These results support the idea of an evolutionary link between RE viruses and type C mammalian viruses.